The long-term goal of this project is to understand factors required for the establishment and maintenance of renal epithelial cell phenotypes. We have developed a technique to isolate and grow human renal progenitor cells in vitro which are capable of being stimulated to develop into epithelial phenotypes. Additionally, we have recently established that immortal cell lines derived from Wilms' tumor can respond to proliferation and differentiation agents. This presents the exciting new potential to systematically examine at the molecular level, the putative mechanisms involved in the processes of renal progenitor cell induction, lineage commitment, and epithelial differentiation of the nephron. An understanding of these processes would shed light not only on normal (and abnormal) renal development but also on the maintenance of phenotype in adults, and its modification during renal epithelial repair and tumor formation. Our hypothesis is that retinoic acid responsive proteins play an important role in renal development and epithelial differentiation. We plan to use responsive primary and immortalized human renal progenitor cells as well as the SK-NEP-l Wilms' tumor cell to delineate the precise temporal changes in gene and protein expression when renal precursor cells are induced to form epithelial condensates, and then to distict epithelial cell lineages. Additionally, we plan to examine if retinoids have a role in lineage specification or in the maintenance of the renal proximal tubule phenotype in mature kidneys.